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Human p32 protein relieves a post-transcriptional block to HIV replication in murine cells

Nature Cell Biology volume 5, pages 611–618 (2003)Cite this article

An Addendum to this article was published on 01 September 2003

Abstract

In the mouse, replication of human immunodeficiency virus type 1 (HIV) is blocked at the levels of entry, transcription and assembly. For the latter effect, the amounts of unspliced viral genomic RNA could have an important function. Indeed, in murine cells, HIV transcripts are spliced excessively, a process that is not inhibited by the murine splicing inhibitor p32 (mp32). In marked contrast, its human counterpart, hp32, not only blocks this splicing but promotes the accumulation of viral genomic transcripts and structural proteins, resulting in the assembly and release of infectious virions. A single substitution in hp32 of Gly 35 to Asp 35, which is found in mp32, abrogates this activity. Thus, hp32 overcomes an important post-transcriptional block to HIV replication in murine cells.

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Figure 1: Analysis of HIV mRNA species in infected cells.
Figure 2: Suboptimal effects of Rev in murine cells and its inhibition by ASF/SF2 in primate cells.
Figure 3: hp32 rescues the effects of Rev in murine cells.
Figure 4: Gly 35 in hp32 is critical for its effects on pCMV128 in murine cells.
Figure 5: hp32 increases levels of unspliced viral transcripts and their stability in murine cells.
Figure 6: hp32 increases production of HIV in murine cells.

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Acknowledgements

We thank D. Irwin for excellent technical assistance. We thank A. Adachi and K. Tokunaga for pNL-CAT (pNLenCAT) proviral clone, N. Landau for pNL-Luc (pNL-luc-E−R−) proviral clone and MGT5 cell line, A. Krainer for p32 and ASF/SF2 cDNAs, P. Bieniasz for pBS/HIV(78-340), and the National Institutes of Health (NIH) AIDS Research and Reference Reagent Program for various reagents. This work was supported by Research Grants from the NIH (B.M.P.), California University-wide AIDS Research Program (B.M.P., Y.-H.Z.) and a training grant from the NIH (Y.-H.Z.).

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  1. Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, Mt. Zion Research Building Room N231, 2340 Sutter Street

    Yong-Hui Zheng, Hai-Feng Yu & B. Matija Peterlin

  2. University of California, San Francisco, 94115, CA, USA

    Yong-Hui Zheng, Hai-Feng Yu & B. Matija Peterlin

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Correspondence to B. Matija Peterlin.

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Zheng, YH., Yu, HF. & Peterlin, B. Human p32 protein relieves a post-transcriptional block to HIV replication in murine cells. Nat Cell Biol 5, 611–618 (2003). https://doi.org/10.1038/ncb1000

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